GENETICS AND GENOMIC MEDICINE
AROUND THE WORLD
Genetics and genomic
medicine in Morocco: the
present hope can make the
future bright
Khadija Belhassan1 Karim Ouldim1 &
Abdel Aziz Sefiani2
1
Medical Genetics and Onco-Genetics Department, Hassan II
University Medical Center, Fez, Morocco
2
Medical Genetics Department, National Institute of Hygiene, Rabat,
Morocco
Correspondence
Khadija Belhassan, MD, Medical Genetics and Onco-genetics Unit, Central Laboratory of Medical Analysis, Hassan II University Medical Center, PB:
1835, Atlas, Fez 30000, Kingdom of Morocco; Tel: (+212) 535 61 90 52; Fax: (+212) 535 61 90 53; academic E-mail: khadija.belhassan@usmba.
ac.ma
doi: 10.1002/mgg3.255
Introduction
The status of medical genetics and genomics medicine in
Morocco cannot be truly understood without considering
the general health system components in the country,
policy making, social factors, cultural behaviors, and even
historical events, within the geographic state. It is important to note that medical genetics does not operate in a
vacuum, but with all of these factors in a symbiotic
relationship.
General Statistics, Geography,
History, and Political Overview
The kingdom of Morocco occupies 710.850 square kilometers, spanning from the Mediterranean Sea and Atlantic Ocean on the north and the west, respectively, into
the borders of Algeria and Mauritania on the East and
south. A large mountainous area occupies the interior
body of the country, with a desert area in the far south.
Morocco is located in the extreme northwest of Africa at
the doors of continental Europe. The Mediterranean
Strait of Gibraltar opens Moroccan territories to the
European continent via Spain (Charoute et al. 2014;
Geography of Morocco, 2016) (Figure 1).
The Moroccan Monarchy called “Allawi Monarchy” has
reigned over Morocco since the 17th century. The kingdom became a French protectorate in 1912, and gained
independence in 1956. Since its independence, Moroccan
domestic and foreign policies have focused on
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maintaining Morocco unity and working toward peace in
the Middle East. (James 2016; The World of Royalty,
2016).
As of 2014, the population of Morocco was estimated to
be 33,848,242. About 58% of the population is urban.
(royaume du Maroc, 2016). Urban migration has been
steadily increasing over the last two decades, increasing
from 51.5% to 55% between 1994 and 2004 and then to
58% in 2014. This phenomenon presents a serious problem for policy planners due to the heavy stress it places on
services in major cities (Morocco Health Ministry, 2013).
Morocco’s birth rate stood at 18.8 per 1.000, whereas
the death rate was reported at 5.6 per 1.000, with a projected annual growth rate of 1.09%. The population up to
age 60 years is expected to reach a percentage of 11.5%
by the year 2020, while the population less than 15 years
will reach 20.9% in 2030.
The vast majority of the population is Muslim; the
other small religious groups represent Jews and Christians. The ethnic population diversity includes mainly
Arabs, Berbers, and Hassani (Sahrawi), with some individuals of Phoenicians, Romans, Vandals, Byzantines,
Moriscos, sub-Saharian Africans, and European remnants
of the colonial period (Ratbi et al. 2008; Morocco Health
Ministry, 2013).
Morocco is a country of immigrants: nearly 1.8 million
Moroccans live abroad, in particular in France, Italy,
Spain, and Belgium (Ratbi et al. 2008).
Analphabetism decreased from 55% to 43% from 1994
to 2004.
ª 2016 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use,
distribution and reproduction in any medium, provided the original work is properly cited.
K. Belhassan et al.
Genetics and Genomic Medicine Around the World
Figure 1. Morocco Territory Map, with its geographic opening to the European continent.
Morocco’s general health policy focuses on the promotion of primary health care, encouragement of family
planning especially in rural areas, and the reduction in
infant and maternal mortality (Morocco Health Ministry,
2013).
Economy, Education Policies
The agricultural sector contributes 19% to the national
GDP, 15% in agriculture and 4% in agribusiness. This
sector employs over 4 million rural persons and creates
about 100,000 jobs in the field of food. The income of
80% of the rural populations depends on agriculture.
Agriculture accounts for between 14 and 24% of total
imports and between 15 and 21% of total exports
(Moroccan National Gate, 2016).
The long coastline of 2945 km length makes the fisheries sector an important part of the economy. Other natural resources include wood and minerals (phosphates,
iron, manganese, lead, and zinc) (Moroccan National
Gate, 2016).
Morocco has identified tourism as a priority sector in
its development strategy. (Moroccan National Gate, 2016)
This Tourism program, developed jointly by private sector operators and government, has concentrated on road
network development, placing Morocco among the first
African countries to have such infrastructure. Sixty per
cent of its 60.000 km road network is surfaced, whereas
1500 km of roads are built every year. In addition, the
Mediterranean by-pass is under construction (Moroccan
National Gate, 2016).
Morocco continues to stress the importance of education in social development and economic growth. The
government advocates for free basic education especially in
rural areas with a promotion of girls’ education. (Moroccan
National Gate, 2016) 61.5% of the population over the age
of 10 years is without any formal educational qualifications, while 30.5% have either a primary or fundamental
school certificate. Only 8% have a high school degree
education or more (Morocco Health Ministry, 2013).
From a social standpoint, nearly 5 million Moroccans
live in substandard housing. This situation does not only
distort and disfigure the Moroccan urban landscape, but
also it is the bed of the proliferation of many social illnesses. A project, spearheaded by The National Initiative
for Human Development, has been undertaken to eradicate slums, to provide adequate housing for individuals in
proportion to their resources and to provide economic
opportunities (Moroccan National Gate, 2016).
Health Care System in Morocco
According to the World Health Organization, the health
system includes all activities, formal or informal, which
focuses on health services available to a population to
meet their needs in terms of health. The role of any
health system is to first identify the needs of its population and to secondly implement the policies and actions
that can meet that needs (World Health Organization
about Morocco, 2016).
The Morocco health care system is based upon the
principles of solidarity and social cohesion. The system is
characterized by universal health insurance for Moroccans, with public financing of primary health care, and an
orientation care network focused on population health
needs. This system is structured by levels with territorial
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and regional organization, a public/private partnership,
an intersector collaboration, and a specialization of general practitioners in the primary health care (Morocco
Health Ministry, 2016).
A compulsory health coverage system (AMO) and
regime of health assistance (RAMED) (for the benefit of
deprived persons based on the principles of social cohesion and national solidarity) were, respectively, created in
2005 and 2011, to provide universal access to health care.
Both systems cover approximately 60% of the population
(Morocco Health Ministry, 2016).
The health global spending reached approximately 47.8
billion Dirhams in 2010, or 1498 Dirhams per capita (181
US dollars in 2010). These expenses represent 6.2% of the
Gross Domestic Product, compared to 5.3% in 2006
(Morocco Health Ministry, 2013).
For a population of about 33 million, the number of
physicians is 19.770, whereas nurses account for 29.025
(Morocco Health Ministry, 2013).
The number of urban basic health care facilities is
2689, whereas the number of rural basic health care facilities is 1938, providing a basic health care center per
12.000 habitants (Morocco Health Ministry, 2013).
There are 33 local hospital, 25 regional hospital centers,
and five university hospital centers, with two others under
constructions. (Morocco Health Ministry, 2013).
There are four specialized laboratory centers for dealing
with tuberculosis, family planning, diagnostics, and cancer
screening. (Morocco Health Ministry, 2013).
Chronic diseases accounts for 18% affecting mainly
females and elders, thus, the health system priorities are
fighting chronic diseases such as diabetes and arterial
hypertension. The system aims also to prevent infectious
diseases by immunization program implementation, and
treating sexually transmitted infections (Morocco Health
Ministry, 2013).
Other priority areas are providing free cancer treatment, especially for breast and cervical cancer, and reducing infant mortality. In Morocco, out of every 1000
liveborn children, 29 infants die before reaching one year,
19 during the first month of life and 10 between the 1st
and 12th months. Thus, in 1000 infants aged one year,
two do not reach their 5th year. The probability a child
dies before reaching 5 years is 30 for 1000. To address
this issue, there are programs to reduce maternal mortality rates by providing free childbirth delivery, to encourage breast feeding, and to provide adequate nutritional
intake; 3.1% of children are underweight (Morocco
Health Ministry, 2013).
The Moroccan national household mean size is 4.9.
Fecundity has diminished to 2.5 children due to contraception and marriage age increase. 56.6% of the population up to 15 years is married.
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Access to water, electricity and sanitation is also a priority for the health system (Morocco Health Ministry,
2013).
Medical Genetics in Morocco, a
Population Marked by High
Consanguineous Marriage Rate
Medical genetics is a new specialty in Morocco, recognized since 1996. Thus, Morocco is among the first countries to have recognized this specialty, just after France
since 1995.
The pioneer and first medical geneticist in the country
is Dr. Abdel Aziz Sefiani, head of the Department of
Medical Genetics in Rabat National Institute of Hygiene.
Since then, other departments have been established. A
Department of Genetics in Casablanca faculty of medicine was established followed by another one in Fes
Hassan II University medical center. Less than 30 Medical genetics practitioners and trainees are enrolled in the
field. The specialty is blossoming in five university medical centers; more medical geneticists will turn to this
specialty which is a mixture of medical practice and
research. In addition two international university hospitals in Casablanca and Rabat, with both public/private
partners are adopting medical genetics in their facility.
Ideally, Moroccan geneticists will establish university
hospital medical genetics units with reference centers in
the various domains of medical genetics. To accomplish
this, it is necessary to increase the number of medical
geneticists in Morocco.
Consanguinity
Like many North African or Middle Eastern groups where
the consanguinity rate is increased, Morocco consanguineous marriages account for 19.9–28% of all marriages, with 50% of these between first cousins.
(Tadmouri et al. 2009) A recent study estimates the frequency of consanguineous marriages to be 59.09% among
families with autosomal recessive disorders (Jaouad et al.
2009). Despite this high rate of consanguinity, information on inherited disorders in Morocco is not extensive.
There are only few detailed studies on the prevalence of
some diseases such as familial Mediterranean fever, cystic
fibrosis, and beta thalassemia. Nevertheless, an important
sporadic data are available for more than 250 genetic diseases and syndromes (Ratibi et al. 2008; Charoute et al.
2014). Despite the lack of genetic diseases epidemiological
surveillance, they occupy a more and more important
sphere in morbidity, but they stimulate only a humble
interest in Moroccan health care system strategy. Birth
defects, inborn errors of metabolism, mitochondrial
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diseases, primary immunodeficiency, hereditary diseases,
and cancers affect thousands of children and adults, and
are a source of both economic and psychological burden
for families. Raising awareness of these disorders is a key
need.
Diagnostic tests
The Moroccan newsletter “Liberation” reported in 1993
on the first molecular genetic test performed in the
Moroccan National Institute of Hygiene to diagnose
Duchenne Muscular Dystrophy. It was an ambitious,
optimistic step for this new field of Medical Genetics and
molecular biology in the country. Since then, several
genetic tests have been developed and patients with common genetic or inherited diseases in Morocco can benefit
from genetic diagnosis (Table 1).
It is important for families and physicians to realize the
importance of a diagnosis, even if the child dies. A diagnosis will allow more appropriate genetic counseling
where recurrence rates can be discussed. Some genetic
diseases are well known, identified well and easy to diagnose by the practitioners on the basis of their clinical
expertise and without resorting to expensive equipment.
Others will require the support of specialized examinations or imaging, or genetic biochemical analyses to end
up with a precise diagnosis. Genetic diseases are not registered within the framework of the Moroccan health policy; they are, however, recognized as a problem of public
health by specialists working with many patients with
genetic illness.
With all the challenges facing the medical genetics field
in Morocco, the first genetics health care professionals in
the country were been promoting the field and trying to
offer services to a population neglected by the health system. The limited resources, especially in an era of new
generation sequencing, leave many genetic conditions
undiagnosed, including those contracted in daily routine
practice such as: Autism, although no exact statistics
about the prevalence of the disorder in Morocco exist,
support groups were created to allow the parents of autistic children to meet each other in order to exchange
experiences and create awareness about autism. Type1
diabetes, where the genetic predisposition is elucidating
more about the disease and should consequently be taken
into consideration by the country health program.
Hemophilia, According to the World Health Organization, more than 3000 people suffer from hemophilia in
Morocco. Unfortunately, this number still is too low for
the disease to be a priority of the Moroccan health system. Nevertheless, without adapted management, the
hemophilia quickly becomes a handicap and a real ordeal
for whole family. The primary preventive strategy
Genetics and Genomic Medicine Around the World
represents the best alternative. In Morocco, the cost of
antihemophilic factors is particularly costly and cannot be
afforded by most families. Only in case of emergency,
treatment can be delivered. Primary Immunodeficiency,
Morocco is sorely lacking units and health care professionals specialized in management of children suffering
from primary immunodeficiency. There are only two
medical professional specialized in this field in the whole
country, a very insufficient number with regard to the
increasing number of children suffering from PID. An
adequate bone marrow transplantation platform is absent
in the country. Every month the health care system witnesses powerlessly the agony of one to two children
because that system does not have the means to handle
their illnesses. While in other countries such as Tunisia
and Saudi Arabia, the children suffering from these
pathologies can receive a transplant and live a normal life.
It is urgent to react to improve an intolerable situation
by setting up quickly units specialized to improve significantly the quality of life of these children. Sexual Differentiation Disorders, hundreds of cases are encountered
in the Moroccan health facilities. This figure is, however,
far from reflecting the reality because most of the parents
and people affected by these disorders do not consult the
specialized centers. Many parents refuse categorically the
idea that their boys, raised as boys since their birth, are
in fact girls. For them, it is a real drama to see their child
changing sex specially that they do not consult at an early
stage of the disorder. The decision of a surgical operation
should be taken in dialog with the doctors of various specialties who estimate, in the light of the biological,
anatomical, genetic, and psychological data which they
have, the chances of success of such intervention, then
with the parents of the child. This approach allows minimizing the risks related to the impact of sex reparation
on the child. Some individuals have attempted suicide
because they were conflicted over their new identity.
Pediatricians and the general practitioners have an
important role in the diagnosis of the disorders and the
orientation of the children and the parents toward the
specialized centers. Congenital skeletal malformations,
many skeletal malformations are genetic or inherited.
Prenatal diagnosis can be made by the ultrasound. The
shock of the announcement of a deformation, the possibilities of management of this deformation explain the
importance of the prenatal consultations and genetic
counseling. Congenital heart defects, with a rough frequency of 8 for 1000 births, constitutes one of the first
causes of infant mortality in Morocco, and remains a
considerable cause of handicap of the child and the
young adult. Although the cause may remain unknown
in many cases, genetic causes, in particular chromosomal
aberrations such as trisomy 21, will account for a
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Table 1. Twenty years of cytogenetics molecular cytogenetics and molecular biology in Morocco.
Disease
Diagnosis method
Constitutional chromosomal abnormalities
Williams syndrome
Digeorge syndrome
Prader Willi and Angelman syndromes
Cytogenetic and molecular cytogenetics
Cytogenetic and molecular cytogenetics (FISH)
Cytogenetic and molecular cytogenetics (FISH)
Cytogenetics molecular cytogenetics and molecular biology
(methylation status of 15q11.2)
Cytogenetic and molecular cytogenetics
Molecular biology of (BCR/ABL: by RT-PCR)
Molecular biology (V617F mutation in JAK2 gene)
Molecular biology of (Exon 9 of CALR gene)
Molecular biology (MEFV gene)
Molecular biology (SGCG gene/525 delT mutation)
Molecular biology
Molecular biology
Molecular biology of (GJB2 gene/35delG mutation)
Molecular biology
Molecular biology of (Moroccan recurrent mutations)
Molecular biology of (Exon 10 of CFTR gene)
Molecular biology of (MYH gene/Moroccan recurrent Mutations)
Molecular biology of (IDUA gene/c.3233C>G mutation)
Molecular biology of (Moroccan recurrent mutations)
Molecular biology of (XPC gene/c.1643_1644delTG mutation)
Molecular biology of (AGXT gene/p.Ile244Thr mutation)
Molecular biology of (FGFR3 gene)
Molecular biology of (HFE gene: C187G and G845A mutations)
Molecular biology of Y chromosome deletions (AZF)
Molecular biology of (recurrent deletion of NPHP1 gene)
Molecular biology (Moroccan recurrent mutations)
Molecular biology analysis of IL28B gene
Molecular biology (AURKC gene: c.144delC mutation)
Chronic myeloid leukemia
Chronic myeloid leukemia
Myeloproliferative syndromes
Myelofibrosis with myeloid metaplasia, essential thrombocythemia
Familial Mediterranean fever
Autosomal recessive Limb-Girdle muscular dystrophy type 2C
Muscular dystrophy Duchenne and Becker type
Spinal muscular atrophy
Deafness due to connexin 26 anomalies
Factor V Leiden mutation
Beta-thalassemia and hbb-related diseases
Cystic fibrosis
Attenuated familial adenomatous polyposis
Mucopolysaccharidosis type 1
Glycogen storage disease type IA
Xeroderma pigmentosum
Hyperoxaluria
Achondroplasia and hypochondroplasia
Hemochromatosis
Male infertility
Nephronophtisis
Familial hypercholesterolemia
Pharmacogenetics
Molecular diagnosis of male infertility associated with large-headed
multiflagellar polyploid spermatozoa
significant number. Prenatal diagnosis represents an
essential aspect in preventing cardiac birth defects. Heart
surgery requires an adapted infrastructure, a multidisciplinary team and the development of specialized surgical
skills. Management of congenital heart diseases thus represents a heavy cost, out of reach for the majority of
the patients still not benefiting from health coverage
(Doctinews, 2016).
As awareness of genetic disorders has increased both
within the general population and among health care providers, interest in genetics has increased. Many genetic
diseases are responsible for a very high mortality rate, and
the high infant mortality can be explained partly due to
undiagnosed genetic disease. The media in Morocco has
tried to disseminate genetic information about lysosomal
storage diseases, glycogen storage diseases, and inborn
errors of metabolism in a country that lacks enzyme
replacement therapy and reliable centers for bone marrow
engraftment. Until recently, the Morocco ministry health
system did not adopt strategies specific to control genetic
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conditions; many patients affected by these diseases are
managed by cooperative medical societies and nongovernmental associations (Table 2).
New Born Screening and Genetic
Counseling
According to the international projections, the number of
newborns with a genetic condition in Morocco will be
5% (Dr Anwar Cherkaoui, 2001).
Management of genetic conditions can be laborious
and expensive. Some of these diseases are chronic and
require therapeutic strategies which can cost up to 100
000 Dirhams a month. The costs are too much to be covered by health insurance, much less most families. Until
now, families are left to their own destiny. The situation
is even worse for families with multiple affected members.
When will Morocco take care of these patients? A prevention policy costs less than a management one, but,
Where? How? Who? When?
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In this context, it is clear that Morocco with its national
health policies should quickly start to integrate a strategy of
prevention and raising awareness that genetic diseases are a
serious health issue. The systematic screening of certain
genetic diseases is not practiced in Morocco, but some pilot
studies have been conducted, in particular for congenital
hypothyroidism. The problem of the systematic screening
is not the screening in itself rather the necessary logistics
and the budget for a real national program which would
support it. Newborn screening requires a great infrastructure to ensure collection of appropriate samples from all
newborns that are then forwarded to reference laboratories,
recontact of infants that screen positive, arranging diagnostic testing, and then management of the positive cases.
Ethically, it is not reasonable to screen for certain
genetic diseases while being unable to treat or effectively
manage already diagnosed patients. A targeted screening
and prevention strategy toward high-risk families at risk
to have another affected child can be adopted to avoid
this possible fact.
The diagnosis of a genetic disease sometimes requires
expensive examinations tools, such as Exome Sequencing.
Thus, certain genetic diagnostic tools are expensive, or
even not available in Morocco, especially enzymology
examinations and NGS examinations, but there is tendency to forget the cost of the undiagnosed such as: hospitalizations expenses, and families’ useless unlimited
travel expenses, which could be avoided in many cases.
(Morocco genetic team personal experience).
Genetic counseling
Given all the boundaries cited previously about the high
morbidity of genetic diseases, the lack of understanding of
genetics and genetic disease in both the general population,
and the medical profession, health system priorities which
exclude genetic diseases from their medical strategies, the
country economic limitation resources, and the heavy burden of genetic disease diagnosis and management, genetic
counseling can be an important tool for families. Genetic
Genetics and Genomic Medicine Around the World
counseling is particularly important in Morocco when considering the high rate of consanguineous matings. A prophetic Islamic religious text says: “Choose well your mate
(for your gamete) as (the hidden) traits can reappear.”
Some affected families may believe they got the illness
as a punishment from God, others consider it as God’s
test or message, and they react differently dealing with
the situation, by different mature and immature self-ego
defense mechanisms. They tend to condemn the opposite
side, to fear stigmatization, or to reject the whole situation by putting the affected child in an orphan center.
Genetic counseling can help individuals understand
inheritance patterns and the risk of genetic disease in
consanguineous marriages. We have seen many families
with three or four affected children and who declare
they would not have had additional children if they had
been warned from the first birth about a risk related to
consanguinity. Thus genetic counseling is not only about
assessing medical risk, it is about using psychology and
knowledge about social and cultural issues to empower
families to help them make the most appropriate decisions for their family. The low literacy in Morocco may
foster a low understanding of genetic concepts, but, on
the other hand, geneticists have poor skills simplifying
the material as to be received easily by patients. This is
due to the fact that in Morocco, there is no specialization in genetic counseling, geneticist have to be the
genetic counselor often with no psychological skills
background. Another big issue involves the unavailability
of formal legislation regulating the practice of genetics,
and unavailability of alternative choices for families,
either by preimplantation genetic diagnosis, or prenatal
genetic diagnosis (Morocco medical genetics team personal experience).
Medical Genetics Legislations and
Reproductive Law
With the fast continuous advances in genetics and genomic technologies, ethical issues emerge, and bring to the
Table 2. Nongovernmental institutions offering services for patients with genetic conditions.
Association
Targeted population
Moroccan society of medical genetics
Moroccan society of clinical chemistry and medical biology(SMCC-BM)
Mirror association for autistic child
Hemophilic Moroccan association
Moroccan association of autoimmune and systemic diseases (AMMAIS)
Overcome autism association
Pediatrics Moroccan association
Pediatric ORL Moroccan association
Moroccan association against myopathy (AMM)
Population with genetic conditions
Population with metabolic conditions
Population with autism
Population with hemophilia
Population with autoimmune and systemic diseases
Population with autism
Children including those with primary immune deficiency
Population including congenital deafness
Population with myopathies
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surface the immense need to set up regulations which
would frame and supervise the practice of genetics in
Morocco. Since the government cannot afford financially
all aspect of genetics, it has at least the obligation to set
up regulations for the private sector that are investing in
the field. Regulations have to include genetic test charges
and ensuring that testing laboratories have necessary practice approvals, have a trained staff and are awarded a
diploma for genetics practice.
On July 15th, 2014, the Moroccan Minister for Health
presented in a press release its intention to forbid the free
sale of DNA tests by Internet means and for paternity test
in particular. The lack of legal framework and the potential misuse of the test by a man who wants to avoid parental responsibilities based on a negative test were areas
of concern. The Moroccan justice approved only two laboratories in the whole country for judicial DNA tests, one
in Rabat and the other one in Casablanca. (Pauline
Chambost, 2014). This is a step to ensure quality control
with regards to genetic tests.
Historically, abortion was legal only when it constituted
a necessary measure to protect the health of the mother
(Dr Anwar Cherkaoui, 2001). The revision of Islamic prophetic texts about embryo creation, lead some scholars to
say that it is not forbidden to have abortion before the
first 4-month is finished, but that after the completion of
4 months, abortion is forbidden. They rely on a prophetic
text saying: “Verily, each of you is brought together in his
mother’s abdomen for forty days in the form of a drop of
fluid. Then it is a clinging object for a similar [period].
Thereafter, it is a lump looking like it has been chewed for
a similar [period]. The angel is then sent to him and he
breathes into him the spirit”.
On June 9th, 2016 the Council of government adopted
the new penal code which expands abortion rights, this
penal law will be reviewed by Parliament room for admission. Abortion will be legal in three cases: when the woman
is a victim of rape or incest after opening of a judicial
inquiry, when she is affected by mental disorders (but the
list of these disorders was not defined in the bill yet),
and finally in case of fetal deformation. The national order
of doctors will have to define the precise list of the
deformations.
In the first two cases, the abortion has to take place
within 90 days after the beginning of the pregnancy. In
case of fetal malformation, the abortion can be made
before the 120th day of pregnancy, even more when the
disease needs more time to be delineated but without
exceeding 22 weeks. In every case, the pregnancy termination has to be made by a doctor in a public hospital center or in an approved private Hospital (Reda Zaireg
2016) (Table 3).
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Pharmacogenomics, Personalized
Medicine, Genetic Predisposition to
Tuberculosis, and Lab
Standardization
Pharmacogenomics is the collective effect of the genome
on drug metabolism, related to personalized medicine,
with the aim of defining for each patient the most appropriate treatment suitable for his genetic characteristics
and biological particularities.
Morocco is an endemic country of tuberculosis. To
develop new preventive and therapeutic strategies, it is
important to understand the pathophysiology of the disease. Thus the identification of genetic factors predisposing to tuberculosis is fundamental. Among the factors
that explain the large individual variability in responding
to Mycobacterium tuberculosis, the role of the host genetic
factors is elucidated. Through numerous association studies performed in Morocco, the interaction between host
and bacterium in this disease opens the door to personalized medicine which can be extrapolated to other genetic
conditions and personalized drug response (El Baghdadi
et al. 2013).
It is imperative that laboratories provide high quality,
reliable, and accurate testing. Today, Moroccan biologists
have to be dynamic in driving their labs toward the
international certification ISO9001, even toward the
accreditation according to the standard ISO 15189.
Recently the Moroccan newsletter “Liberation” in 2015
has published the news of ISO 9001 certification for
Rabat National Institute of Hygiene operating many biological tests including genetic testing.
Research in Genetics
Fes University of Al-Qarawiyin built in 859, by Fatima
Al-Fihri, has the distinction of being the world’s very first
university. Yes, it was a Muslim woman who pioneered a
model of higher learning coupled with the issuance of
degrees of various levels. Pope Sylvester II graduated from
the same university and was the first to introduce Arabic
numerals to medieval Europe. One of the university’s
most famous students was a Jewish physician and
philosopher, Maimonides (Joseph and Najmabadi 2003;
Swartley 2005).
Research in Morocco is investigator-driven without
input from the government regarding research priorities.
Research funding relies on international, formal or informal, scientific cooperation. The latter exists mainly with
France (Mina Kleiche, 2002). Some diagnostic and research
services offered to patients are sustained by small networks
with international cooperation. Some Moroccan genetic
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Table 3. Abortion policy in the previous and the new penal code article.
Abortion policy penal
law article
Previous 453 penal
law article
2016 new penal law
article
Grounds on which
abortion is permitted
Necessary measure to
protect the health of
the mother
Necessary measure to
protect the health of
the mother
Pregnancy results from a
Rape or crime of incest
Mother with mental
illness
Fetus with grave
malformations
Fetus with genetic
conditions
departments are connected to Orphanet (European reference portal network for information on rare diseases and
orphan drugs), or associated with INSERM (French
National Institute of Health and Medical Research).
The Human Molecular Genetics Unit at Morocco Pasteur Institute can be used as an example of genetic
research in Morocco. This unit focuses on molecular
investigation of hereditary deafness, type 2 diabetes and
the role of the Y chromosome in sex determination and
male infertility. Knowing that Human mutation databases
can be divided into general, locus-specific, and national
and ethnic mutation databases, this lab has the mission to
collect and document mutations and frequencies of polymorphisms reported in Moroccan population (mainly
from published articles available in Pub Med and other
online resources). This data collection, the Moroccan
Genetic Disease Database (MGDD,) is an open resource
available for researchers and clinicians in an easy web-based
access: http://mgdd.pasteur.ma/ (Claustres et al. 2002;
Stenson et al. 2003; Hamosh et al. 2005) (Figure 2 and
Table 4).
The Mediterranean Founder Mutation Database
(MFMD) is another example of Moroccan genetics initiative to offer web-based access to founder mutation information of the country’s Mediterranean population: http://
mfmd.pasteur.ma/. This database contains 383 founder
mutations found in 210 genes related to 219 diseases and
provide an overview about the migration history of the
Mediterranean population (Charoute et al. 2015).
To recapitulate, medical and genetics researchers in
Morocco are in general struggling to conduct their
research. Morocco, as part of the Arab world and
Conditions
-
3 days delay to think about a decision
Information about abortion risk
Information about judicial procedures if choice to keep pregnancy
Abortion have to be done in a public hospital or accredited clinic
Abortion have to be done before 90 days of pregnancy
Husband consent
Parents consent if mother unmarried
Legal tutor consent
Legal institution consent
Abortion before 120 days of pregnancy’
List of malformations not yet established
Abortion before 120 days of pregnancy
List of genetic conditions not yet established
Table 4. MGDD presentation of the highest mutations and polymorphisms rate attributed to some genetic condition (Charoute et al.
2014).
Diseases
Susceptibility to type 2 diabetes
mellitus (T2DM)
Susceptibility to familial breast
ovarian cancer 2
Susceptibility to spermatogenic
failure
Susceptibility to familial breast
ovarian cancer 1
Ataxia-telangiectasia
Beta thalassemia
Susceptibility to Mycobacterium
tuberculosis
Phenylketonuria
Primary congenital A glaucoma 3
Retinoblastoma
Mutation
Polymorphism
Total
0
43
43
10
22
32
0
29
29
4
21
25
14
18
0
11
0
16
25
18
16
14
11
11
0
0
0
14
11
11
according to the 2013 Scimago Institutions Rankings
report, was ranked as having a weak output and of low
scientific impact (El-Azami-El-Idrissi et al. 2013; ScimagoLab, 2013).
Table 5 displays some genetics literature starting from
1988 with genetics linkage analysis, and continuing
recently with some important publications in different
genetics subdivisions and using new emerging genetic
technologies. Enormous amounts of Moroccan genetics
studies require international collaboration as NGS and
Array CGH are still unavailable in the country
(Table 5).
ª 2016 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
595
Genetics and Genomic Medicine Around the World
K. Belhassan et al.
Figure 2. MGDD general statistics, disorders percentage according to the mode of inheritance (Institut Pasteur Maroc, 2016).
Table 5. Genetics studies and literature using PubMed scientific publications Browser (Sefiani et al. 1988; Tajir et al. 2012; Grant et al. 2013;
Makrythanasis et al. 2014; Mansouri et al. 2014; Natiq et al. 2014; Qrafli et al. 2014, 2014; Janati Idrissi et al. 2015; Ratbi et al. 2015; Twigg
et al. 2015; Elalaoui et al. 2016; Guaoua et al. 2016; Jouali et al. 2016).
Author
Title
Genetics method
Field
Year
Guaoua S et al.
NAT2 Genotypes in Moroccan Patients with
Hepatotoxicity Due to Antituberculosis Drugs.
Further evidence of POP1 mutations as the cause of
anauxetic dysplasia.
First application of next-generation sequencing in
Moroccan breast/ovarian cancer families and report of
a novel frameshift mutation of the BRCA1 gene.
Acromelic frontonasal dysostosis and ZSWIM6
mutation: phenotypic spectrum and mosaicism.
TPMT alleles in Moroccan.
Sanger sequencing and real-time
polymerase chain reaction.
Sanger sequencing
Pharmacogenetics
2016
Mendelian genetics
2016
NGS-targeted sequencing
Cancer genetics
2016
NGS and deep sequencing for
mosaicism evaluation
Allele-specific PCR and PCR-RFLP
genotyping
Exome sequencing
Mendelien genetics
2016
Pharmacogenetics
2015
Metabolic genetics
2015
Sanger sequencing
Mendelian genetics
2014
Exome sequencing with Array
CGH
Mendelien genetics
2014
Cytogenetics, molecular
cytogenetics, array CGH, Methyl
PCR
Real Time PCR and RFLP-PCR
genotyping
Positional-cloning approach for
linkage-disequilibrium mapping
of an identified susceptibility
locus in chromosomal region.
Sanger sequencing
Clinical Cytogenetics
2014
Genetic association
studies
Genetics Linkage
analysis
2014
Mitochondrial
genetics
Genetic linkage
analysis
2012
Elalaoui SC et al.
Jouali F et al.
Twigg SR et al.
Janati Idrissi M et al.
Ratbi I et al.
Mansouri M et al.
Makrythanasis P
et al.
Natiq A et al.
Qrafli M et al.
Grant AV et al.
Tajir M et al.
Sefiani A et al.
Heimler Syndrome Is Caused by Hypomorphic
Mutations in the Peroxisome-Biogenesis Genes PEX1
and PEX6.
A novel nonsense mutation in SCN9A in a Moroccan
child with congenital insensitivity to pain.
Diagnostic exome sequencing to elucidate the genetic
basis of likely recessive disorders in consanguineous
families.
A new case of de novo 19p13.2p13.12 deletion in a
girl with overgrowth and severe developmental delay.
The CYP7A1 gene rs3808607 variant is associated with
susceptibility of tuberculosis in Moroccan population.
Age-dependent association between pulmonary
tuberculosis and common TOX variants in the 8q1213 linkage region.
Pyruvate dehydrogenase deficiency caused by a new
mutation of PDHX gene in two Moroccan patients.
Linkage studies do not confirm the cytogenetic
location of incontinentia pigmenti on Xp11.
Historically, Moroccans were pioneers in several scientific domains. To promote medical research in Morocco,
serious efforts and several strategic goals must be agreed
596
X chromosome DNA probes
2013
1988
on by all stakeholders, scientists, and decision makers.
The strategy should include upgrading research infrastructure and equipment, providing sufficient funds and
ª 2016 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
K. Belhassan et al.
high-quality training, as well as promoting excellence.
Additionally, scientists working abroad should be seen as
an asset. A medical research council – inspired from the
US National Institutes of Health, the Medical Research
Council in the UK, and INSERM in France – is necessary
to establish strategies that promote medical and health
research in collaboration with international institutions
(El-Azami-El-Idrissi et al., 2013; ScimagoLab. 2013).
Recently, in 2016, new research genetic centers are
emerging either by the endorsement of the kingdom’s
highest authority or by private institutions. Three examples are highlighted:
● Princess Lalla Salma, chairwoman of the Lalla Salma
Foundation for Cancer Prevention and Treatment,
inaugurated the First Cancer Research Institute in
Africa. This institute was created as part of a public
interest group represented by Fes Hassan II University
hospital center, Fes Sidi Mohammed Ben Abdallah
University and Lalla Salma Foundation (Foundation
Lalla Salma, 2016)
● A partnership between Rabat Abulcasis Health Sciences
International University (UIASS) and Paris (Imagine)
Institute of genetic diseases, the main genetic research
institute in France. The objective aims to better understand genetic diseases, bringing diagnostic, and therapeutic solutions to Moroccan patients and their
families (Doctinews, 2016)
● A laboratory of genetic engineering will be created at Fes
Euro-mediterraneenne University. A framework agreement was signed between Dassault systems and the ministry of the Higher education. This agreement has the
objective of creating treatments for diseases from which
the African population suffers (Doctinews, 2016)
Conclusion
Genetics is a rapidly evolving field relying on technological advances and with a direct effect on society.
Nevertheless, in Morocco, it is difficult to establish – if
impossible outside very specialized departments – a
diagnosis for many genetic conditions and to obtain
exact data on prevalence of these diseases. According to
international projections, the number of newborns who
are or will be affected by genetic diseases is considered
to be 5% in Morocco. Morocco needs to invest in
genetics research, diagnosis of genetic disorders and
clinical genetics services, including genetic counseling to
help its citizens who are living with or at risk for
genetic disorders. As Marc Levy stated, “The loss of a
child is a wound which never heals; La perte d’un enfant
est une plaie qui ne cicatrise jamais; ‫ﻓﻖﺩﺍﻥ ﻃﻒﻝ ﺟﺮﺡ ﻻ‬
‫”ﻳﻦﺩﻡﻝ‬
Genetics and Genomic Medicine Around the World
References
Charoute, H., H. Nahili, O. Abidi, K. Gabi, H. Rouba, M.
Fakiri, et al. 2014. The Moroccan Genetic Disease Database
(MGDD): a database for DNA variations related to inherited
disorders and disease susceptibility. Eur. J. Hum. Genet.
22:322–326.
Charoute, H., A. Bakhchane, H. Benrahma, L. Romdhane,
K. Gabi, H. Rouba, et al. 2015. Mediterranean Founder
Mutation Database (MFMD): taking advantage from
founder mutations in genetics diagnosis, genetic diversity
and migration history of the Mediterranean population.
Hum. Mutat. 36:E2441–E2453.
Claustres, M., O. Horaitis, M. Vanevski, and R. G. Cotton.
2002. Time for a unified system of mutation description and
reporting: a review of locus-specific mutation databases.
Genome Res. 12:680–688.
Doctinews. 2016. Revue d’information medicale destinee aux
professionnels de la sante qui se distingue par sa
presentation journalistique. Official website:
www.doctinews.com.
Dr Anwar Cherkaoui. 2001. Le conseil genetique, une
orientation pour les familles a risque. Economiste
newsletter. Le 09/02/2001. Edition N°:954.
El Baghdadi, J., A. V. Grant, A. Sabri, S. El Azbaoui, H. Zaidi,
A. Cobat, et al. 2013. Genetique humaine de la tuberculose.
Pathol. Biol. 61:11–16.
Elalaoui, S. C., F. Z. Laarabi, M. Mansouri, N. A. Mrani, G.
Nishimura, and A. Sefiani. 2016. Further evidence of POP1
mutations as the cause of anauxetic dysplasia. Am. J. Med.
Genet. A 170:2462–2465.
El-Azami-El-Idrissi, M., M. Lakhdar-Idrissi, K. Ouldim, W.
Bono, A. Amarti-Riffi, M. Hida, et al. 2013. Improving
medical research in the Arab world. Lancet 382:2066–2067.
Foundation Lalla Salma. 2016. Prevention et traitement des
cancers. Princess Lalla salma and the inauguration of the
first Cancer Research Institute in Africa. contrelecancer.ma/
en/media/2016/03/08/inauguration-de-linstitut-de-recherchesur-le-cancer.
Geography of Morocco. 2016. Available at: en.wikipedia.org
website.
Grant, A. V., J. El Baghdadi, A. Sabri, S. El Azbaoui, K.
Alaoui-Tahiri, I. A. Rhorfi, et al. 2013. Age-dependent
association between pulmonary tuberculosis and common
TOX variants in the 8q12-13 linkage region. Am. J. Hum.
Genet. 92:407–414.
Guaoua, S., I. Ratbi, O. El Bouazzi, S. Hammi, A. Tebaa, J. E.
Bourkadi, et al. 2016. NAT2 genotypes in Moroccan patients
with hepatotoxicity due to antituberculosis drugs. Genet.
Test. Mol. Biomarkers. doi:10.1089/gtmb.2016.0060.
Hamosh, A., A. F. Scott, J. S. Amberger, C. A. Bocchini, and
V. A. McKusick. 2005. Online Mendelian Inheritance in
Man (OMIM), a knowledgebase of human genes and
genetic disorders. Nucleic Acids Res. 33:D514–D517.
ª 2016 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
597
Genetics and Genomic Medicine Around the World
K. Belhassan et al.
Institut Pasteur Maroc. 2016. Moroccan Genetic Disease
Database Official website: mgdd.pasteur.ma/statistics.php
James, N. S. 2016. Morocco: challenges to tradition and
modernity. 2nd edn. ISBN: 978-1-138-82826-1(hbk).
Routledge, USA.
Janati Idrissi, M., I. Samri, Y. Khabbal, M. El Hassouni, and K.
Ouldim 2015. TPMT alleles in the Moroccans. Clin. Res.
Hepatol. Gastroenterol. 39:e55–e56.
Jaouad, I. C., S. C. Elalaoui, A. Sbiti, F. Elkerh, L. Belmahi, A.
Sefiani 2009. Consanguineous marriages in Morocco and the
consequence for the incidence of autosomal recessive
disorders. J. Biosoc. Sci. 41:575–581.
Jouali, F., F. Z. Laarabi, N. Marchoudi, I. Ratbi, S. C. Elalaoui,
H. Rhaissi, et al. 2016. First application of next-generation
sequencing in Moroccan breast/ovarian cancer families and
report of a novel frameshift mutation of the BRCA1 gene.
Oncol. Lett. 12:1192–1196.
Makrythanasis, P., M. Nelis, F. A. Santoni, M. Guipponi, A.
Vannier, F. Bena, et al. 2014. Diagnostic exome sequencing
to elucidate the genetic basis of likely recessive disorders in
consanguineous families. Hum. Mutat. 35:1203–1210.
Mansouri, M., S. Chafai Elalaoui, B. Ouled Amar Bencheikh,
M. El Alloussi, P. A. Dion, A. Sefiani, et al. 2014. A novel
nonsense mutation in SCN9A in a Moroccan child with
congenital insensitivity to pain. Pediatr. Neurol. 51:741–744.
royaume du Maroc. 2016. Haut-commissariat au plan:
governmental website. Available at: www.hcp.ma
Mina Kleiche. 2002. la science en Afrique a l’aube du 21eme
siecle sous la direction de Roland Waast et jacques
gaillard aide n° erbic 18 ct 98 9164 commissions
europeennes, dg xii subvention n° 98 01 49 800 ministere
des affaires etrangeres, France. la recherche scientifique au
Maroc 3° partie.
Mina Kleiche. 2002. la science en Afrique a l’aube du 21eme
siecle Sous la Direction de Roland Waast et Jacques Gaillard
Aide N° ERBIC 18 CT 98 9164 Commission Europeenne,
DG XII Subvention N° 98 01 49 800 Ministere des Affaires
Etrangeres, France. La recherche scientifique au Maroc 1°
partie: histoire et institutions.
Mina Kleiche. 2002. la science en Afrique a l’aube du 21eme siecle
sous la direction de Roland Waast et jacques gaillard aide n°
erbic 18 ct 98 9164 commissions europeennes, dg XII
subvention n° 98 01 49 800 ministere des affaires etrangeres,
France. la recherche scientifique au Maroc 2° partie.
Moroccan National Gate. 2016. Governmental website.
Available at: http://www.maroc.ma/en ‫ﺍﻝﺑﻮﺍﺏﺓ ﺍﻝﻭﻁﻧﻲﺓ‬.
Morocco Health Ministry. 2010. COMPTES NATIONAUX DE
LA SANTE 2010 Royaume du Maroc Ministere de la Sante
juin 2013 Depot legal: 2009MO3281 ISBN: 9981-06-821-6.
Morocco Health Ministry. 2016. Governmental website:
manual guides. Available at: www.sante.gov.ma/Publications/
Guides-Manuels/Pages/default.aspx
Natiq, A., S. C. Elalaoui, S. Miesch, C. Bonnet, P. Jonveaux, S.
Amzazi, et al. 2014. A new case of de novo 19p13.2p13.12
598
deletion in a girl with overgrowth and severe developmental
delay. Mol. Cytogenet. 7:40.
Pauline Chambost. 2014. Le ministere de la Sante veut interdire
les tests ADN en ligne. TelQuel.ma Newsletter. Juillet 16 2014.
Qrafli, M., Y. Amar, J. Bourkadi, J. Ben Amor, G. Iraki, Y.
Bakri, et al. 2014. The CYP7A1 gene rs3808607 variant is
associated with susceptibility of tuberculosis in Moroccan
population. Pan Afr. Med. J. 18:1.
Ratbi, I., A. E. Gati, and A. Sefiani. 2008. The Moroccan
human mutation database. Indian J. Hum. Genet. 14:106–107.
Ratbi, I., K. D. Falkenberg, M. Sommen, N. Al-Sheqaih, S.
Guaoua, G. Vandeweyer, et al. 2015. Heimler syndrome is
caused by hypomorphic mutations in the peroxisomebiogenesis genes PEX1 and PEX6. Am. J. Hum. Genet.
97:535–545.
Ratibi, I., et al. 2008. Cystic fibrosis in Morocco, where are the
patients? J. Cyst. Fibros. 7:440–443.
Reda Zaireg. 2016. Avortement, peines alternatives,
enrichissement illicite: Les nouveautes du code penal. AL
HUFFINGTION POST Maghreb. 26/05/2016.
ScimagoLab. 2013. Forecasting exercise: how world scientific
output will be in 2018. Available at: www. scimagolab.com/
blog/2012/forecasting exercise-how-world-scientific coutput-will-bein-2018/(accessed September 3, 2013).
Sefiani, A., D. Sinnett, L. Abel, S. Szpiro-Tapia, S. Heuertz, I.
Craig, et al. 1988. Linkage studies do not confirm the
cytogenetic location of incontinentia pigmenti on Xp11.
Hum. Genet. 80:282–286.
Stenson, P. D., E. V. Ball, M. Mort, A. D. Phillips, J. A. Shiel, N.
S. Thomas, et al. 2003. Cooper DN Human Gene Mutation
Database (HGMD): 2003 update. Hum. Mutat. 21:577–581.
Suad, J., and N. Afsaneh. 2005. Encyclopedia of Women &
Islamic Cultures: Economics, education, mobility and space.
Brill Academic Publishers, Netherlands. p. 314. ISBN
9789004128200.
Swartley, K. E.. 2005. Encountering the world of Islam.
BottomLine Media, India. p. 74; ISBN 13: 9780989954501.
Tadmouri, G. O., P. Nair, T. Obeid, M. T. Al Ali, N. Al Khaja,
and H. A. Hamamy. 2009. Consanguinity and reproductive
health among Arabs. Reprod. Health. 6:17.
Tajir, M., J. B. Arnoux, A. Boutron, S. C. Elalaoui, P. De
Lonlay, A. Sefiani, et al. 2012. Pyruvate dehydrogenase
deficiency caused by a new mutation of PDHX gene in two
Moroccan patients. Eur. J. Med. Genet. 55:535–540.
The World of Royalty. 2016. Available at: www.royalty.nu/
Africa/Morocco.html
Twigg, S. R., L. B. Ousager, K. A. Miller, Y. Zhou, S. C.
Elalaoui, A. Sefiani, et al. 2016. Acromelic frontonasal
dysostosis and ZSWIM6 mutation: phenotypic spectrum and
mosaicism. Clin. Genet. 90:270–275.
World Health Organization about Morocco. 2016. Available at:
www.who.int/countries/mar/en
ª 2016 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.